WO 2004/080492 A1 discloses a method for radiofluorination of a biological targeting vector, comprising reaction of a compound of formula (I) with a compound of formula (II):

or,
a compound of formula (III) with a compound of formula (IV)

wherein:                R1 is an aldehyde moiety, a ketone moiety, a protected aldehyde such as an acetal, a protected ketone, such as a ketal, or a functionality, such as diol or N-terminal serine residue, which can be rapidly and efficiently oxidised to an aldehyde or ketone using an oxidising agent;        R2 is a group selected from primary amine, secondary amine, hydroxylamine, hydrazine, hydrazide, aminoxy, phenylhydrazine, semicarbazide, and thiosemicarbazide and is preferably a hydrazine, hydrazide or aminoxy group;        R3 is a group selected from primary amine, secondary amine, hydroxylamine, hydrazine, hydrazide, aminoxy, phenylhydrazine, semicarbazide, or thiosemicarbazide, and is preferably a hydrazine, hydrazide or aminoxy group;        R4 is an aldehyde moiety, a ketone moiety, a protected aldehyde such as an acetal, a protected ketone, such as a ketal, or a functionality, such as diol or N-terminal serine residue, which can be rapidly and efficiently oxidised to an aldehyde or ketone using an oxidising agent;        
to give a conjugate of formula (V) or (VI) respectively:

wherein X is —CO—NH—, —NH—, —O—, —NHCONH—, or —NHCSNH—, and is preferably —CO—NH—, —NH— or —O—; Y is H, alkyl or aryl substituents; and
the Linker group in the compounds of formulae (II), (IV), (V) and (VI) is selected from

wherein:
n is an integer of 0 to 20;
m is an integer of 1 to 10;
p is an integer of 0 or 1;
Z is O or S.
Poethko et al [J. Nucl. Med., 45(5), 892-902 (2004)] disclose a method of radiolabelling peptides with the radioisotope 18F, wherein an aminooxy-functionalised peptide is condensed with [18F]-fluorobenzaldehyde to give a labelled peptide having an oxime ether linkage as follows:

Schottelius et al [Bioconj. Chem., 19(6), 1256-1268 (2008)] further developed the method of Poethko et al. Schottelius et al use an aminooxy-functionalised peptide wherein the amine of the aminooxy group is protected with an N-Boc (Boc=tert-butyloxycarbonyl) protecting group. The desired aminooxy-functionalised peptide is generated in situ in the presence of [18F]-fluorobenzaldehyde via deprotection of the N-Boc group at acidic pH (pH=2) at 75° C. Schottelius et al use a 5-fold molar excess of the Boc-protected precursor, because the deprotection was not quantitative under the reaction conditions.
Mezo et al [J. Pept. Sci., 17, 39-46 (2010)] describe some of the problems associated with the above oxime ligation chemistry of Boc-protected aminooxy-functionalised peptides. Thus, it is known that the initially formed free aminooxy-peptide can acylate unreacted Boc-protected aminooxy-peptide, leading to undesirable by-products. It is also known that the reactivity of the free aminooxy group of the functionalised peptide is high towards carbonyl compounds. Consequently, unwanted condensation can occur with any adventitious aldehydes or ketones present either in the reaction mixture or in any subsequent purification steps. Such aldehydes or ketones could be traces of acetone present in the solvents used, or formaldehyde (eg. from plasticizers). Mezo et al are interested in solving this problem for both the conjugation of anti-cancer drugs and of [18F]-fluorobenzaldehyde to peptides. Mezo et al solve the problem by carrying out the deprotection of the Boc-aminooxy peptide in the presence of a tenfold molar excess of free (aminooxy)acetic acid (Aoa) as a ‘carbonyl capture agent’. The deprotected aminooxy-peptide and excess Aoa is then lyophilised and stored at 4° C. Immediately prior to the oxime ligation reaction, the lyophilised mixture is reconstituted, and excess Aoa is separated by HPLC or Sep-Pak plus C18 cartridge. Mezo et al provide an example in which non-radioactive (i.e. 19F) 4-fluorobenzaldehyde is conjugated to an aminooxy-functionalised somatostatin peptide using this technique. Mezo et al do not provide any data on 18F-radiolabelling.
There is therefore still a need for improved methods of radiolabelling peptides and other biological targeting molecules.